Volunteers are being recruited through NIAID's AIDS Vaccine
Evaluation Group (AVEG), which includes six clinical units located in
St. Louis, Nashville, Seattle, Birmingham, Baltimore and Rochester
(NY). These new trials bring the total number of vaccine protocols in
human volunteers conducted through AVEG to 45, using 24 different
vaccine concepts. More than 2,400 volunteers have participated in
AVEG HIV vaccine studies since 1988.
According to Jack Killen, M.D., director of NIAID's Division of
AIDS, "These three trials are part of NIAID's comprehensive
approach to HIV vaccine development. Each of these studies will test
a new idea or approach toward an effective, safe HIV vaccine."
In AVEG 027, an experimental HIV vaccine already being
studied as an injected product will be applied to specific mucosal
sites, for example, the moist tissues lining the respiratory, urinary
and reproductive tracts. Later, antibodies will be measured at those sites.
Most HIV infections, such as those acquired through sexual exposure,
are transmitted across mucosal surfaces. A vaccine that induces
mucosal antibodies may work better than other types of vaccines
against this most common form of exposure.
In AVEG 028, a new strategy -- based on the common
Salmonella bacteria -- will be used to present HIV proteins to the
immune system. Because this bacteria normally reproduces only
inside human cells, it can present the HIV proteins in a way that may
better induce immune responses.
In AVEG 033, a novel adjuvant, GM-CSF, is being combined
with a canarypox virus-based vector containing HIV proteins.
GM-CSF is a drug commonly used to improve blood cell production in
cancer patients. This study will determine if GM-CSF can improve the
immune response to the vector.
Additional information about each trial follows.
AVEG 027 is evaluating sequential doses of live recombinant
canarypox ALVAC-HIV vCP205 delivered first by injection and then
via the mucosa.
ALVAC-HIV vCP205 is made from a weakened canarypox
virus used as a vaccine for birds. The canarypox virus can fit large
pieces of foreign DNA in its genome, infect human cells and cause
them to produce foreign proteins. ALVAC-HIV vCP205 contains
copies of genes for three pieces of HIV -- the surface protein, the core
protein and one enzyme -- more than any other experimental
preventive HIV vaccine tested so far. When the ALVAC vaccine
infects human cells, the cells make proteins from the genes and
package the proteins into HIV-like particles called pseudovirions.
Although not infectious, these pseudovirions fool the immune system
and trigger an immune response. ALVAC-HIV vCP205 has already
been tested in more than 700 volunteers in other AVEG studies.
Eighty-four volunteers will receive the vaccine or a placebo
control at entry, one, three and six months. Volunteers will first
receive an intramuscular injection to prime the immune response
before being given booster doses either intramuscularly or via a
swab, nose drops or other method through a variety of mucosal
routes: oral, vaginal, nasal and rectal. This is the first study in
humans to examine vaginal, nasal and rectal administration of an HIV
ALVAC vCP205 is being supplied by Pasteur Merieux
Connaught. The study is being conducted at all six AVEG sites: the
University of Alabama at Birmingham, the University of Rochester
Medical Center, the University of Washington, Johns Hopkins
University, Vanderbilt University and the University of St. Louis.
Peter Wright, M.D., of Vanderbilt University, chairs the study.
AVEG 028 applies a new vector vaccine approach to HIV
vaccine research. Vector vaccines use a non-disease-causing virus
or bacteria to transport HIV or other foreign genes into the body. In
this case, one protein from HIV (gp120) is inserted into the
Salmonella bacteria to make the vaccine, called VVG203. VVG203
was genetically engineered at the University of Maryland Center for
Vaccine Development in Baltimore to make it incapable of growing or
multiplying in humans.
Live-vector approaches offer many advantages including the
ability to induce long-lasting antibody and cell-mediated immune
responses and the relatively low cost of production. In addition,
because the vaccine is administered orally, it may stimulate the
production of mucosal antibodies. Previous studies conducted by the
AVEG have used vaccinia and canarypox viruses as vectors. Unlike
vaccinia, however, the Salmonella in this vaccine has been modified
so it does not reproduce in human cells, which is an important safety
AVEG 028 will assess if the VVG203 vaccine is safe and how
the body's immune system responds to the vaccine when it is given
alone or sequentially with another AIDS vaccine, HIV-1 MN rgp120.
The study will also determine the optimal dose and immunization
schedule. The trial will enroll 47 adults at low risk of HIV infection.
All six AVEG sites are participating in this study. Mary Lou
Clements-Mann, M.D., M.P.H., of Johns Hopkins University, is the
study chair. Both vaccines used in this study are manufactured by
VaxGen of South San Francisco, Calif.
AVEG 033 uses a new adjuvant with ALVAC to attempt to
induce better immune responses. An adjuvant enhances or modifies
the immune-stimulating properties of a vaccine. The only licensed
adjuvants for use in human vaccines are alum compounds. Alum
may act in part by stimulating certain chemical messengers, called
In this study volunteers are being given a recombinant
cytokine, human granulocyte-macrophage colony stimulating factor
(GM-CSF), as the adjuvant. GM-CSF may elicit a stronger immune
response than alum when given directly with a vaccine.
GM-CSF is presently used to boost blood cell counts in
transplant and cancer patients. It also can increase the ability of
important immune system cells known as antigen presenters to
initiate and direct immune responses. When used as an adjuvant,
GM-CSF may enhance both antibody and cellular responses to the
vaccine. The vaccine being used in AVEG 033 is ALVAC-HIV
vCP205, which primarily stimulates the cellular immune response.
The study investigators will evaluate the ability of GM-CSF to enhance
both cellular and antibody responses to vCP205. The 36 volunteers
enrolled in the study will be followed for 18 months.
The study is being conducted at four AVEG sites: the
University of Alabama at Birmingham, the University of Rochester
Medical Center, Johns Hopkins University and Vanderbilt University.
Thomas Evans, M.D., of the University of Rochester Medical Center,
chairs the study. GM-CSF is being supplied by Immunex (Seattle),
and ALVAC-HIV vCP205 is being supplied by Pasteur Merieux
Connaught (Lyon, France).
More information about these trials can be obtained by calling
the AIDS Clinical Trials Information Service (1-800-TRIALS-A)
or by visiting their Web site at http://www.actis.org.
NIAID, part of the National Institutes of Health (NIH), supports
biomedical research to prevent, diagnose and treat illnesses such as
AIDS, tuberculosis, malaria, asthma and allergies. NIH is an agency
of the U.S. Department of Health and Human Services.
Press releases, fact sheets and other NIAID-related materials are
available via the NIAID home page at http://www.niaid.nih.gov.